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Definition, incidence (CUP = cancer of unknown primary) Heterogen group of metastatic tumors, when the origin (primary) of tumor can not be detected by standard diagnostic tests (physical exam., lab, occult blood test, IHC, X-ray, CT, mammography (MR, PET)). 3-5 %- of all malignancies most common malignancy Majority of primery tumor can not be detected in vivo

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CUP Biology Biologic behaviour is less known than in the case of known primary tumors More involved field, early dissemination, lack of primary tumor (regression?, dormant tumor?), unpredictable metastatic spread, agressivity Metastatic disease could arise without primary tumor growth (organ specific transformation of circulating tumor cells, onkogen induction) Prognosis usually worse But: There is a small, heterogen subgroup, where prognosis is much better, long term survival is possible, even cure sometimes!

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Treatment of unfavorable group Realistic aim: decrease symptoms and maintain quality of life -Survival improvement is minimal Systemic treatment or best supportive care -Low toxicity, well tolerated, relatively convenient chemotherapy first line -Second line treatment : only in selected cases -Most common combinations: 3 weekly paclitaxel+carboplatin, cisplatin+gemcitabine, or cisplatin+etoposid.